Daytime sleepiness and risk of coronary heart disease and stroke: results from the Nurses’ Health Study II

Highlights

• Daytime sleepiness associated with higher risk of cardiovascular disease (CVD) and stroke.

• Daytime sleepiness associated with sleep parameters and metabolic abnormalities.

• Sleep and metabolic variables explain daytime sleepiness and CVD/stroke association.

Abstract

Objective

The objective of this study was to determine whether daytime sleepiness is independently associated with coronary heart disease (CHD) and stroke or whether the positive association is explained by short sleep duration, disturbed sleep, and circadian disruption, conditions that are associated with cardiometabolic risk factors for vascular events.

Methods

Longitudinal analyses of data from the Nurses’ Health Study II comprising 84,003 female registered nurses aged 37–54 at baseline were conducted in 2001 with follow-up until 2009. Multivariate Cox regression was used to explore the relationship between reported daytime sleepiness and the incidence of either CHD or stroke (n = 500 cases).

Results

Women who reported daytime sleepiness almost every day, compared with rarely/never, had an elevated adjusted risk of cardiovascular disease (CVD) (hazard ratio (HR) = 1.58, 95% confidence interval (CI) 1.15–2.17). Controlling for sleep variables (sleep duration, snoring, shift work, and sleep adequacy) or potential metabolic biological mediators of disrupted sleep (diabetes, hypercholesterolemia, and hypertension) appreciably attenuated the relationship (HR = 1.17, 95% CI 0.84–1.65; and HR = 1.34, 95% CI 0.97–1.85, respectively). Controlling for both sleep variables and metabolic risk factors eliminated an independent association (HR = 1.09, 95% CI 0.77–1.53). A similar pattern was observed for CHD and stroke individually.

Conclusions

Daytime sleepiness was not an independent risk factor for CVD in this cohort of women, but rather, was associated with sleep characteristics and metabolic abnormalities that are risk factors for CVD.

Introduction

Daytime sleepiness, defined as the inability to stay awake and alert during the major waking periods of the day, resulting in unintended lapses into drowsiness or sleep [1], has been estimated to affect about 20% of adults [2]. Excessive daytime sleepiness is a significant public health concern since it is associated with cognitive impairment, automobile accidents, injuries, medical errors, and lost productivity [3].

Multiple studies have also found daytime sleepiness to be associated with the incidence of stroke and coronary heart disease (CHD) (Table 1) [4], [5], [6], [7], [8], [9]. Three primary explanations for this association have been proposed. First, daytime sleepiness could be symptomatic of insufficient sleep, disturbed sleep, and/or circadian disruption that in turn increase the risk of vascular events [4], [5]. Second, daytime sleepiness could be due to an underlying medical illness that is a risk factor for cardiovascular disease (CVD) (including either stroke or CHD) [7], [8]. Third, daytime sleepiness could be an independent risk factor for stroke and CHD [7].

Prior studies have had significant limitations in exploring an independent association between daytime sleepiness and CVD. If daytime sleepiness is an independent risk factor, then the association should remain significant after controlling for sleep and circadian disturbances and other risk factors for CVD. However, many previous studies did not have measures of important sleep characteristics including sleep duration [5], [6], [7], [8], [9], insomnia [4], [9], or snoring [4] and no previous studies had measures for shift work. Further, most of the studies conceptualized the variables indicative of insufficient or disturbed sleep only as potential interaction variables whereby they explored whether the absence, presence, or degree of presence of these variables affected the strength of the association between daytime sleepiness and vascular events, rather than fully controlling for them [4], [5], [6], [8], [9]. Only one study of elderly subjects reported results that included snoring and insomnia in fully adjusted multivariate models [5]. Several studies failed to control for key cardiovascular risk factors: two of the studies did not control for depression [4], [6] and two did not control for blood pressure, hypercholesterolemia, or diabetes [5], [6]. Finally, whether there are sex differences in the relationship between sleep and CVD has not been fully explored. Three of the studies did not report results from stratified analyses by sex to determine the unique association between daytime sleepiness and cardiovascular events in women [4], [6], [9].

The Nurses’ Health Study II (NHS-II) provides a unique opportunity to explore the association between daytime sleepiness and CVD in women because it includes measures of daytime sleepiness, sleep parameters (sleep duration, snoring, sleep sufficiency, and shift work), as well as cardiovascular risk factors in a large and well-characterized sample of younger females followed longitudinally. We hypothesized that daytime sleepiness would be associated with increased risk of stroke and CHD, and we aimed to determine whether the association would be primarily explained by insufficient or disturbed sleep and by other risk factors for CVD.